TheIn VivoResponse of Foetal Tendons to Sutures
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The in vivo response of foetal flexor digitorum profundus tendons to tendon sutures was studied macroscopically and microscopically in foetal lambs. No tendon adhesions were noted at any of the examination intervals. 4 days after injury, a mild inflammatory reaction was noted around the suture. The tendon examined at the 4-week interval showed evidence of migration of epitenon cells from the outer surface of the tendon into the suture track. The tendon examined at the 6-week interval showed normal tendon fibres surrounding the suture site. Differences between foetal skin and foetal tendon healing are discussed along with the possible role of amniotic fluid in modulating the healing process in the foetus.Cite
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The scintigraphic results of three methods of labeling red blood cells (RBCs) were compared. Image quality was evaluated in 200 patient studies by measuring the left ventricle to background ratio. These studies were performed using either the in vivo, modified in vivo or in vitro method for labeling RBCs. The average ventricle to background ratio for the in vitro method was 2.85 compared to 2.42 and 2.20 for the modified in vivo and in vivo methods, respectively. The in vitro method gave a statistically higher ratio than did either the in vivo or the modified in vivo methods.
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L1210 murine leukemic cells were serially passaged in BDF1 mice and were treated in vivo with methotrexate (MTX) and 2,4-diamino-5-(3',4'-dichlorophenyl)-6-methylpyrimidine (DDMP) alone or in combination. The time course of emergence of resistance of the treated cell lines was studied both in vivo and in vitro. When used as a single drug, in vivo resistance to MTX developed gradually and was considerable at eight passages and complete by 11 passages. Complete in vivo resistance to DDMP used alone occurred by the fifth passage. Complete in vivo resistance to the drugs in combination was seen by the eighth passage. In cells demonstrating complete DDMP resistance, as determined in vivo, there was no evidence of cross-resistance to MTX measured either in vivo or in vitro, while MTX resistance was associated with incomplete cross-resistance to DDMP. The greatest degree of resistance, as determined in vitro, occurred in the cell line treated with the drug combination. In vitro tests of drug resistance correlated well with in vivo survival data. An important observation was that major in vivo drug resistance was accompanied by only a small measurable effect using standard in vitro screening techniques. The implications of this finding are discussed.
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The in vivo response of foetal flexor digitorum profundus tendons to tendon sutures was studied macroscopically and microscopically in foetal lambs. No tendon adhesions were noted at any of the examination intervals. 4 days after injury, a mild inflammatory reaction was noted around the suture. The tendon examined at the 4-week interval showed evidence of migration of epitenon cells from the outer surface of the tendon into the suture track. The tendon examined at the 6-week interval showed normal tendon fibres surrounding the suture site. Differences between foetal skin and foetal tendon healing are discussed along with the possible role of amniotic fluid in modulating the healing process in the foetus.
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In vitro determination of metabolic stability is routinely used to assess the overall metabolic liability of compounds and for prioritization for in vivo studies. If in vitro metabolic stability data could be used to reliably predict in vivo clearance (CL), it would add significant value in the selection of compounds for in vivo pharmacokinetic and pharmacology studies. We have evaluated the utility of our in vitro metabolic stability screening assay to estimate in vivo CL in the mouse. The in vitro mouse clearances (CLin vitro) of 146 structurally diverse compounds with metabolic stabilities > 30 %, were compared to mouse in vivo CL data. Approximately 45 % of the compounds showed agreement between in vivo CL and predicted CLin vitro within a 2-fold error criteria. The correlation appeared worse when correction for the extent of incorporation of plasma protein binding or both plasma and S9 bindings (i.e. ~14 % and~ 28 % agreement, respectively). Classification of the compounds into three groups based on in vivo CL (<30 mL/min/kg, 30-70 mL/min/kg, and >70 mL/min/kg) did not show any improvement between in vivo CL and predicted CLin vitro. The percentage of compounds falling within the 2-fold error criteria for low CL, moderate CL and high CL groups were 54, 31 and 24 %, respectively. In conclusion, our analysis suggests that in vitro metabolic stability data, as routinely obtained in early ADME screening protocols, does not demonstrate a strong correlation with or predictivity for, absolute in vivo CL in the mouse.
ADME
Metabolic stability
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Background: Two main factors determine the strength of tendon repair; the tensile strength of material and the gripping capacity of a suture configuration. Different repair techniques and suture materials were developed to increase the strength of repairs but none of techniques and suture materials seem to provide enough tensile strength with safety margins for early active mobilization. In order to overcome this problem tendon suturing implants are being developed. We designed two different suturing implants. The aim of this study was to measure tendon-holding capacities of these implants biomechanically and to compare them with frequently used suture techniques Materials and Methods: In this study we used 64 sheep flexor digitorum profundus tendons. Four study groups were formed and each group had 16 tendons. We applied model 1 and model 2 implant to the first 2 groups and Bunnell and locking-loop techniques to the 3rd and 4th groups respectively by using 5 Ticron sutures. Results: In 13 tendons in group 1 and 15 tendons in group 2 and in all tendons in group 3 and 4, implants and sutures pulled out of the tendon in longitudinal axis at the point of maximum load. The mean tensile strengths were the largest in group 1 and smallest in group 3. Conclusion: In conclusion, the new stainless steel tendon suturing implants applied from outside the tendons using steel wires enable a biomechanically stronger repair with less tendon trauma when compared to previously developed tendon repair implants and the traditional suturing techniques.
Biomechanics
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